Serotonergic System

The human serotonergic system includes at least twelve GPCRs, four ion channel subtypes (5-HT3A, 5-HT3B, 5-HT3C, and 5-HT3E), one transporter, and three enzymes involved in the biosynthesis of serotonin (5-hydroxytryptophan or 5-HT), a monoamine neurotransmitter implicated in such diverse conditions as sleep, anxiety, and obesity. Although serotonin is synthesized in the CNS, it is largely distributed throughout the periphery in neurons of the intestinal myenteric plexus, entero-chromaffin cells, and platelets. The small proportion retained centrally resides in specific neural nuclei. This serotonergic circuit projects throughout the CNS and constitutes the most extensive neurochemical system in the brain.

Pleiotropic responses of serotonin are defined and specificity is determined at the level of distinct GPCRs. The hypothalamic 5HT1B and 5HT2C receptors are principal determinants of feeding behavior and weight control.65 Each receptor appears to serve a discrete role in establishing or sensing satiety through interactions with serotonin, an inhibitor of appetite and feeding. Identification of specific receptor functions has relied on use of agonists66-68 and phenotypic analysis of receptor-null mice.69-72 The 5HT1B-knockout mice eat and grow more than their wild-type counterparts. Absence of the 5HT1B receptor increases weights of select organs but does not promote obesity in the null mice. The 5HT2C-knockout mice are chronically hyperphagic, but they remain relatively lean until developing late-onset obesity. By 10 months, 5HT2C-null mice weighed ~30% more, increased adiposity 40%, and had elevated plasma insulin and leptin levels, 7- and 2.5-fold, respectively, relative to their wild-type counterparts.

It appears that reduced oxygen consumption and energy expenditure contribute to the phenotypic outcomes of the 5HT2C-null mice. Because 5HT1B-knockout mice exhibit stress-related anxiety and 5HT2C-knockout mice are excitable and have disrupted sleep cycles, additional studies are required to elucidate mechanisms underlying the relationship of the serotonergic system, feeding, and energy homeostasis.

100 Weight Loss Tips

100 Weight Loss Tips

Make a plan If you want to lose weight, you need to make a plan for it. Planning involves setting your goals both short term and long term ones. With proper planning, you would be able to have an effective guide on the steps that you want to take, towards losing pounds of weight. Aside from that, it would also keep you motivated.

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